Influenza is caused by an RNA virus of the orthomyxoviridae family. Influenza viruses can be classified into three types (A, B and C), based on antigenic differences in the nucleoprotein and the matrix protein. Influenza A virus is very pathogenic for mammals (e.g. humans, pigs, ferrets, horses) and birds and causes a serious global health concern. Since 1900 over 50 million people have died from influenza.
International patent application No. PCT/CN2010/001187, published as WO 2011/015037, is directed to compounds which exhibit antiviral activity, particularly against influenza virus. In one embodiment, the compounds are heterocyclic amides containing piperazine and isoxazole rings and optionally substituted with one or more substituents. In one embodiment, the compounds described therein are represented by the formula

wherein X, Y, and Z are independently absent or selected from the group consisting of —C(═O)—, —S(═O)—, —SO2—, —N(R12)—, —C(R13)═C(R14)—, and —C(R15R16)n—, n, g, and m are independently 0 to 6; Q and T are independently selected from nitrogen or CR17; and R1-R17 are independently selected from hydrogen, halo, hydroxyl, linear or branched C1-C6 alkyl, linear or branched C1-C6 alkenyl, linear or branched C1-C6 alkynyl, or linear and branched C1-C6 alkoxy, amino, azido, cyano, nitro, nitrile, isonitrile, amide, carboxylate, urea, guanidine, isocyanate, isothiocyanate, and thioether.
International patent application No. PCT/US2011/052965, published as WO/2012/044531, discloses a compound of the formula:

wherein Het is a 5 or 6-membered heterocycle with N, O, or S adjacent to the Ar substituent or adjacent to the point of attachment for the Ar substituent; Ar is aryl or heteroaryl; R is CH3, CH2F, CHF2 or CH═CH2; V is H, CH3 or ═O; W is NO2, Cl, Br, CH2OH, or CN; X is Cl, Br, F, CH3, OCH3, or CN; Y is CH or N; and Z is CH or N, useful in compositions for the prevention and treatment of influenza virus.
There still remains an urgent need for better treatment of viral infections, in particular infections by the influenza virus. Therefore, it is an object of the present invention to provide further antiviral compounds that effectively treat or prevent viral infections, particularly influenza infections, formulations containing these compounds, methods of making the compounds, and methods of using the compounds.